SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24441102
DOI
10.1038/jid.2014.23
PII: S0022-202X(15)36806-8
Knihovny.cz E-resources
- MeSH
- ErbB Receptors metabolism MeSH
- HEK293 Cells MeSH
- Wound Healing MeSH
- Serine Peptidase Inhibitors, Kazal Type MeSH
- Kallikreins metabolism MeSH
- Cathelicidins MeSH
- Antimicrobial Cationic Peptides metabolism MeSH
- Keratinocytes cytology MeSH
- Cloning, Molecular MeSH
- Humans MeSH
- Metalloproteases metabolism MeSH
- Cell Movement * MeSH
- Cell Proliferation MeSH
- Receptors, Purinergic metabolism MeSH
- Gene Expression Regulation, Enzymologic * MeSH
- Recombinant Proteins metabolism MeSH
- Proteinase Inhibitory Proteins, Secretory metabolism MeSH
- Signal Transduction MeSH
- Transfection MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ErbB Receptors MeSH
- Serine Peptidase Inhibitors, Kazal Type MeSH
- Kallikreins MeSH
- Cathelicidins MeSH
- Antimicrobial Cationic Peptides MeSH
- KLK5 protein, human MeSH Browser
- Metalloproteases MeSH
- Receptors, Purinergic MeSH
- Recombinant Proteins MeSH
- Proteinase Inhibitory Proteins, Secretory MeSH
- Spink9 protein, human MeSH Browser
Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived cationic peptide that is found most abundantly in the upper layers of the palmar-plantar epidermis. In vitro, the peptide displays the capacity to inhibit specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells expressing SPINK9 secrete the peptide constitutively. Recombinant SPINK9 (rSPINK9) provoked transactivation of the EGFR in human keratinocytes, resulting in efficient downstream triggering of cell migration. Transactivation occurred via functional upregulation of a disintegrin and metalloproteases (ADAMs), as evidenced by suppression with a metalloproteinase inhibitor and an EGFR-blocking antibody. SPINK9 preparations isolated from human skin also displayed EGFR-transactivating capacity. The classical purinergic receptor antagonists oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4',-disulfonic acid effectively suppressed EGFR transactivation by rSPINK9, indicating that in analogy to what has recently been reported for the cationic antimicrobial peptides cathelicidin LL-37 and bee venom melittin, purinergic receptors have an essential bridging role in promoting the upregulation of ADAM function by the cationic peptide. SPINK9 could represent an example of how a cationic peptide may subserve multiple and interrelated functions that contribute to the maintenance of the physical and immunological barrier of the skin.
See more in PubMed
J Invest Dermatol. 2007 Mar;127(3):594-604 PubMed
Lung Cancer. 2008 Jan;59(1):12-23 PubMed
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11035-9 PubMed
Biol Chem. 2012 Apr;393(5):369-77 PubMed
J Immunol. 2005 Oct 1;175(7):4662-8 PubMed
J Cell Physiol. 1996 Mar;166(3):637-42 PubMed
Mol Cancer Res. 2009 Sep;7(9):1572-81 PubMed
FASEB J. 2010 Dec;24(12):4756-66 PubMed
J Innate Immun. 2012;4(4):377-86 PubMed
Nat Rev Mol Cell Biol. 2005 Jan;6(1):32-43 PubMed
Int Immunol. 2002 Dec;14(12):1415-21 PubMed
J Immunol. 2003 Dec 15;171(12):6690-6 PubMed
FASEB J. 2006 Oct;20(12):2068-80 PubMed
J Invest Dermatol. 2008 Jan;128(1):223-36 PubMed
Blood. 1998 Aug 1;92(3):946-51 PubMed
J Biol Chem. 2010 Mar 5;285(10):7545-55 PubMed
Nat Cell Biol. 2005 Aug;7(8):808-16 PubMed
J Immunol. 2005 Aug 1;175(3):1776-84 PubMed
PLoS One. 2009;4(2):e4372 PubMed
Thromb Haemost. 2013 Sep;110(3):442-9 PubMed
J Invest Dermatol. 2012 Sep;132(9):2129-30 PubMed
J Biol Chem. 1999 Jul 30;274(31):21499-502 PubMed
Immunol Lett. 2006 Jan 15;102(1):98-105 PubMed
Pharmacol Rev. 1998 Sep;50(3):413-92 PubMed
J Invest Dermatol. 2010 Jan;130(1):295-304 PubMed
Nat Commun. 2011;2:229 PubMed
Nat Rev Immunol. 2012 Jun 25;12(7):503-16 PubMed
Med Microbiol Immunol. 2012 Nov;201(4):419-26 PubMed
Int J Biochem Cell Biol. 2002 Jun;34(6):573-6 PubMed
J Invest Dermatol. 2009 Jul;129(7):1656-65 PubMed
J Biol Chem. 2011 Jan 28;286(4):2596-606 PubMed
Science. 1998 Nov 13;282(5392):1281-4 PubMed
Curr Top Microbiol Immunol. 2006;306:27-66 PubMed
J Immunol. 2004 Apr 15;172(8):4987-94 PubMed
J Exp Med. 2012 Jun 4;209(6):1105-19 PubMed
Nat Genet. 2000 Jun;25(2):141-2 PubMed
J Biol Chem. 2008 Nov 7;283(45):30471-81 PubMed
J Biol Chem. 2012 Jul 6;287(28):23678-89 PubMed
Blood. 2001 Jun 15;97(12):3951-9 PubMed
Naunyn Schmiedebergs Arch Pharmacol. 2000 Nov;362(4-5):340-50 PubMed
Science. 1995 Jul 14;269(5221):234-8 PubMed
J Biol Chem. 2005 May 13;280(19):18696-702 PubMed
Cell Immunol. 2012 Nov;280(1):22-35 PubMed
